Department of Pathology and Laboratory Medicine, Women and Infants Hospital, Providence, Rhode Island, USA.
Department of Pathology and Laboratory Medicine, Alpert Medical School at Brown University, Providence, Rhode Island, USA.
Genet Med. 2018 Nov;20(11):1312-1323. doi: 10.1038/gim.2018.22. Epub 2018 Apr 26.
We systematically reviewed the published literature on test failure rates for the sequencing of cell-free DNA (cfDNA) in maternal plasma to identify Down syndrome.
We searched peer-reviewed English publications with diagnostic results on all pregnancies that provided test failure rates. Data on the odds of failure in Down syndrome and euploid pregnancies and the impact of repeat testing were extracted. Random-effects modeling was then used to identify moderators that could explain variability.
Thirty articles satisfied the inclusion criteria for overall failure rates. Study location (Western and Asian with initial testing, and Western with repeat testing) were significant moderators with failure rates of 3.3, 0.6, and 1.2%, respectively (P = 0.001). The odds ratio for Down syndrome in successful versus failed tests was 0.98 (95% confidence interval: 0.62-1.55, I = 0%). Repeat testing from 14 large clinical cohort studies found that 83% (range: 52-100%) of failures were repeated, with 79% (range: 46-97%) being successful.
Lower failure rates in Asian studies may be related to not routinely measuring the fetal fraction and to fewer obese women. Repeat cfDNA testing is effective in providing reliable results after initial failures. Protocols for primary cfDNA screening should focus on Down syndrome, with less common and more structurally abnormal trisomy 18 and 13 pregnancies treated as adjuncts.
我们系统地回顾了已发表的关于母体外周血游离 DNA（cfDNA）测序检测唐氏综合征的文献，以确定其检测失败率。
我们检索了同行评审的英文文献，这些文献提供了所有妊娠的诊断结果，并提供了检测失败率。提取了唐氏综合征和整倍体妊娠失败的可能性以及重复检测的影响的数据。然后使用随机效应模型来确定可以解释变异性的调节因素。
有 30 篇文章符合总体失败率的纳入标准。研究地点（初始检测时的西方和亚洲，以及重复检测时的西方）是显著的调节因素，失败率分别为 3.3%、0.6%和 1.2%（P=0.001）。成功与失败测试中唐氏综合征的比值比为 0.98（95%置信区间：0.62-1.55，I=0%）。来自 14 项大型临床队列研究的重复检测发现，83%（范围：52%-100%）的失败病例被重复检测，其中 79%（范围：46%-97%）为成功。
亚洲研究中的低失败率可能与未常规测量胎儿分数以及肥胖女性较少有关。初次失败后重复 cfDNA 检测可提供可靠的结果。原发性 cfDNA 筛查方案应侧重于唐氏综合征，而较少见且结构更异常的 18 三体和 13 三体妊娠应作为辅助治疗。
